Abstract
BACKGROUND: Dietary n - 3 polyunsaturated fatty acids (PUFAs) were found to be inversely associated with breast cancer risk; however, the underlying pathways between them remain uncertain. We aimed to explore serial mediatory roles of erythrocyte n - 3 PUFAs in association between dietary n - 3 PUFAs and breast cancer risk. MATERIALS AND METHODS: Using a case-control study, 850 cases and 861 controls completed structured questionnaires with dietary information. Erythrocyte n - 3 PUFAs were measured by gas chromatography. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained using multiple unconditional logistic regression models to examine association between dietary n - 3 PUFAs and breast cancer risk. Mediation analyses with bootstrapping were conducted to investigate indirect effects. RESULTS: Higher intake of dietary ALA, long-chain n - 3 PUFAs and total n - 3 PUFAs was associated with lower risk of breast cancer. The adjusted OR (tertile 3 v.1) (95% CI) was 0.70 (0.55, 0.90) for ALA, 0.76 (0.60, 0.97) for long-chain n - 3 PUFAs and 0.74 (0.58, 0.94) for total n - 3 PUFAs, respectively. Mediation analysis showed that erythrocyte long-chain n - 3 PUFAs served as sequential mediators in the relationship between dietary long-chain or total n - 3 PUFAs and breast cancer risk. In particular, erythrocyte long-chain n - 3 PUFAs completely mediated the association between dietary long-chain n - 3 PUFAs and breast cancer risk [indirect effect (95% CI) = -0.982 (-1.529, -0.508)]. The relationship between dietary total n - 3 PUFAs and breast cancer risk was partly mediated by erythrocyte long-chain n - 3 PUFAs [indirect effect (95% CI) = -0.107 (-0.216, -0.014)], accounting for 19.31%. However, the serial mediation model in dietary ALA and risk of breast cancer was not statistically significant [indirect effect (95% CI) = -0.042 (-0.144, 0.049)]. CONCLUSION: This study highlights the complexity and inaccuracy in using a simple analysis of individual dietary n - 3 PUFAs to examine their associations with breast cancer risk without considering the variety of metabolic processes. Interventions aimed at increasing erythrocyte long-chain n - 3 PUFAs may represent a promising strategy for breast cancer prevention.